A Phase 4, Multicenter, Double-blind, Study to Investigate the Efficacy, Safety, and Tolerability of 3 Active Doses of Respreeza® / Zemaira® Weekly Intravenous Infusions Administered Over 3 Years as Longterm Maintenance Therapy in Adult Subjects With Emphysema Related to Alpha1 Antitrypsin Deficiency
Overview
- Phase
- Phase 4
- Status
- Not yet recruiting
- Sponsor
- CSL Behring
- Enrollment
- 270
- Primary Endpoint
- Annual rate of change in adjusted lung density
Overview
Brief Summary
This is a multicenter, parallel-group, double-blind, randomized phase 4 study designed to identify the optimal dose of CE1226 (2 active doses) to slow disease progression as assessed by reduced rates of annual lung density decline in alpha-1 antitrypsin (AAT) deficient participants over 3 years as compared with the marketed dose 60 milligrams per kilogram (mg/kg).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Sponsor will also be blinded to treatment allocation.
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •• Age greater than or equal to (\>=) 18 and less than or equal to (\<=) 65 years at the time of providing written informed consent.
- •• Confirmed diagnosis of emphysema related to AATD with either the PiZZ, PiZ(null), or Pi(null/null) genotype with documented serum AAT levels less than (\<) 11 micrometer (μM) (or \< 50 mg/dL \[milligram/deciliter\]) at any time before the first administration of CE1226 on Day 1 (Baseline).
Exclusion Criteria
- •• Participants should not have acute illness or pulmonary exacerbation within 6 weeks before the first administration of CE1226 on Day 1 (Baseline).
- •• Participants should not have previously received gene therapy for AATD at any point.
- •• Participants with liver disease secondary to AATD.
Arms & Interventions
CE1226 low dose
CE1226 at low dose.
Intervention: CE1226 (Biological)
CE1226 medium dose
CE1226 at medium dose.
Intervention: CE1226 (Biological)
CE1226 high dose
CE1226 at high dose.
Intervention: CE1226 (Biological)
Outcomes
Primary Outcomes
Annual rate of change in adjusted lung density
Time Frame: From Baseline to Month 36
The annual rate of change (expressed as gram per liter per year \[g/L/year\]) in adjusted lung density (15th percentile lung density \[PD15\]) will be calculated on CT scan assessments of whole lung at total lung capacity (TLC).
Secondary Outcomes
- Annual rate of change in forced expiratory volume in 1 second percent predicted (FEV1%)(From Baseline to Month 36)
- Annual rate of change in diffusion capacity of carbon monoxide (DLco)(From Baseline to Month 36)
- Number of severe pulmonary exacerbations(From screening up to Month 36)
- Duration of severe pulmonary exacerbations(From screening up to Month 36)
- Number of participants experiencing treatment emergent adverse events (TEAEs)(From screening up to Month 36)
- Percentage of participants experiencing TEAEs(From screening up to Month 36)